National Human Genome Research Institute
National Human Genome Research Institute
News Article | May 12, 2017
Healthcare professionals now have access to a variety of educational and clinical genomics resources thanks to a new partnership between the National Human Genome Research Institute (NHGRI), part of the National Institutes of Health, and several professional medical societies. The resources are available on the Genetics/Genomics Competency Center (G2C2) website, a free, online collection of more than 500 materials for use in the classroom and for self-directed learning of genetics and genomics concepts for use in the clinic. G2C2 is part of NHGRI's effort to address the growing need among health care professionals for knowledge in genomics, a science that is paving the way for more individualized approaches to detect, treat and prevent many diseases. "G2C2 will be continually updated with new resources for healthcare professionals," said Donna Messersmith, Ph.D., a health policy analyst with NHGRI's Genomic Healthcare Branch, which created the website. "Our goal now is to provide easy access to genomic resources produced by professional societies in different fields of expertise." The website was developed with input from an editorial board of nurses, genetic counselors, physicians, physician assistants and pharmacists. Resources are reviewed by the editorial board for quality and are mapped to published genomic competencies - the knowledge and skills a provider needs to perform specific functions in genomic medicine. In addition to providing an editorial board for content review, the G2C2 team collaborates with NHGRI's Inter-Society Coordinating Committee for Practitioner Education in Genomics (ISCC), which helps facilitate communication around genetics and genomics among practitioner professional societies. To synergize the efforts of ISCC and G2C2, landing pages for professional societies are now available on G2C2. The Association for Molecular Pathology, the National Society of Genetic Counselors, the American College of Clinical Pharmacy, and The Jackson Laboratory are the first organizations to participate in this partnership. ISCC members and others regularly contribute new genomic educational resources to the G2C2 editorial board. "This combined effort brings together both educators and professional societies, whose goals are meeting the specific needs of their discipline," said Robert Wildin, M.D., who heads the Genomic Healthcare Branch at NHGRI. "This synergistic effort advances NHGRI's goal to develop the resources and technology that will accelerate genome research and its application to health care." G2C2 has been updated recently with new resources for a variety of health professionals, including: For more information, visit G2C2 at http://www. . To view resources from a specific organization, visit G2C2, select "Browse Topics" from the menu, and choose one of the organizations.
News Article | May 12, 2017
UNC researchers led the most powerful genomic study of anorexia nervosa conducted to date to identify the common roots anorexia shares with psychiatric and metabolic traits May 12, 2017 CHAPEL HILL, NC - A landmark study led by UNC School of Medicine researchers has identified the first genetic locus for anorexia nervosa and has revealed that there may also be metabolic underpinnings to this potentially deadly illness. The study, which is the most powerful genetic study of anorexia nervosa conducted to date, included genome-wide analysis of DNA from 3,495 individuals with anorexia nervosa and 10,982 unaffected individuals. If particular genetic variations are significantly more frequent in people with a disorder compared to unaffected people, the variations are said to be "associated" with the disorder. Associated genetic variations can serve as powerful pointers to regions of the human genome where disorder-causing problems reside, according to the National Human Genome Research Institute. "We identified one genome-wide significant locus for anorexia nervosa on chromosome 12, in a region previously shown to be associated with type 1 diabetes and autoimmune disorders," said lead investigator, Cynthia Bulik, PhD, FAED, founding director of the UNC Center of Excellence for Eating Disorders and a professor at Karolinska Institutet in Stockholm, Sweden. "We also calculated genetic correlations -- the extent to which various traits and disorders are caused by the same genes," said Bulik. "Anorexia nervosa was significantly genetically correlated with neuroticism and schizophrenia, supporting the idea that anorexia is indeed a psychiatric illness." "But, unexpectedly, we also found strong genetic correlations with various metabolic features including body composition (BMI) and insulin-glucose metabolism. This finding encourages us to look more deeply at how metabolic factors increase the risk for anorexia nervosa," Bulik said. This study was conducted by the Psychiatric Genetics Consortium Eating Disorders Working Group - an international collaboration of researchers at multiple institutions worldwide. "In the era of team science, we brought over 220 scientists and clinicians together to achieve this large sample size. Without this collaboration we would never have been able to discover that anorexia has both psychiatric and metabolic roots," said Gerome Breen, PhD, of King's College London. "Working with large data sets allows us to make discoveries that would never be possible in smaller studies," said Laramie Duncan, PhD, of Stanford University, who served as lead analyst on the project. The researchers are continuing to increase sample sizes and see this as the beginning of genomic discovery in anorexia nervosa. Viewing anorexia nervosa as both a psychiatric and metabolic condition could ignite interest in developing or repurposing medications for its treatment where currently none exist. Institutions that participated in this research include the University of North Carolina at Chapel Hill; Karolinska Institutet; King's College London; Stanford University; the Broad Institute of MIT and Harvard University; Massachusetts General Hospital; Charité-Universtätmedizin Berlin; the department of child and adolescent psychiatry at the University of Duisberg, Essen; and the Wellcome Trust Sanger Institute. Several international funding sources contributed to this work including, but not limited to the National Institute of Mental Health, the Wellcome Trust, the Price Foundation, the Klarman Family Foundation, and the United Kingdom National Institute for Health Research.
Belkaid Y.,U.S. National Institutes of Health |
Segre J.A.,National Human Genome Research Institute
Science | Year: 2014
Human skin, the body's largest organ, functions as a physical barrier to bar the entry of foreign pathogens, while concomitantly providing a home to myriad commensals. Over a human's life span, keratinized skin cells, immune cells, and microbes all interact to integrate the processes of maintaining skin's physical and immune barrier under homeostatic healthy conditions and also under multiple stresses, such as wounding or infection. In this Review, we explore the intricate interactions of microbes and immune cells on the skin surface and within associated appendages to regulate this orchestrated maturation in the context of both host physiological changes and environmental challenges.
Manolio T.A.,National Human Genome Research Institute
New England Journal of Medicine | Year: 2010
Over the past 5 years, genomewide association studies have yielded a wealth of insight into genes and chromosomal loci that contribute to susceptibility to disease. This article, the second in the Genomic Medicine series, describes the design of these studies and considers the extent to which the data they provide are useful in predicting the risk of disease. Copyright © 2010 Massachusetts Medical Society.
Gao B.,National Human Genome Research Institute
Current Topics in Developmental Biology | Year: 2012
Planar cell polarity (PCP), a process controlling coordinated, uniformly polarized cellular behaviors in a field of cells, has been identified to be critically required for many fundamental developmental processes. However, a global directional cue that establishes PCP in a three-dimensional tissue or organ with respect to the body axes remains elusive. In vertebrate, while Wnt-secreted signaling molecules have been implicated in regulating PCP in a β-catenin-independent manner, whether they function permissively or act as a global cue to convey directional information is not clearly defined. In addition, the underlying molecular mechanism by which Wnt signal is transduced to core PCP proteins is largely unknown. In this chapter, I review the roles of Wnt signaling in regulating PCP during vertebrate development and update our knowledge of its regulatory mechanism. © 2012 Elsevier Inc.
Aksentijevich I.,National Human Genome Research Institute
Seminars in Immunopathology | Year: 2015
Autoinflammatory diseases are a genetically heterogeneous group of rheumatologic diseases that are driven by abnormal activation of the innate immune system. Patients present with recurrent episodes of systemic inflammation and a spectrumof organ-specific comorbidities. These diseases are mediated by the overproduction of various inflammatory cytokines, such as IL-1, IL-18, IL-6, TNFα, and type I interferon. Treatments with biologic agents that inhibit these cytokines have been very efficient in most patients. During the past 2 years, remarkable progress has been made in the identification of disease-associated genes owing mostly to new technologies. Next generation sequencing technologies (NGS) have become instrumental in finding single-gene defects in undiagnosed patients with early onset symptoms. NGS has advanced the field of autoinflammation by identifying disease-causing genes that point to pathways not known to regulate cytokine signaling or inflammation. They include a protein that has a role in differentiation of myeloid cells, a ubiquitously expressed enzyme that catalyzes the addition of the CCA terminus to the 3-prime end of tRNA precursors, and an enzyme that catalyzes the oxidation of a broad range of substrates. Lastly, newly described mutations have informed a whole new dimension on genotype-phenotype relationships. Mutations in the same gene can give rise to a range of phenotypes with a common inflammatory component. This suggests greater than anticipated contributions by modifying alleles and environmental factors to disease expressivity. © Springer-Verlag (outside the USA) 2015.
Manolio T.A.,National Human Genome Research Institute
Nature Reviews Genetics | Year: 2013
Genome-wide association studies (GWASs) have been heralded as a major advance in biomedical discovery, having identified ~2,000 robust associations with complex diseases since 2005. Despite this success, they have met considerable scepticism regarding their clinical applicability; this scepticism arises from such aspects as the modest effect sizes of associated variants and their unclear functional consequences. There are, however, promising examples of GWAS findings that will or that may soon be translated into clinical care. These examples include variants identified through GWASs that provide strongly predictive or prognostic information or that have important pharmacological implications; these examples may illustrate promising approaches to wider clinical application. © 2013 Macmillan Publishers Limited. All rights reserved.
Yang Y.,National Human Genome Research Institute
Cell and Bioscience | Year: 2012
Cell signaling mediated by morphogens is essential to coordinate growth and patterning, two key processes that govern the formation of a complex multi-cellular organism. During growth and patterning, cells are specified by both quantitative and directional information. While quantitative information regulates cell proliferation and differentiation, directional information is conveyed in the form of cell polarities instructed by local and global cues. Major morphogens like Wnts play critical roles in embryonic development and they are also important in maintaining tissue homeostasis. Abnormal regulation of these signaling events leads to a diverse array of devastating diseases including cancer. Wnts transduce their signals through several distinct pathways and they regulate vertebrate embryonic development by providing both quantitative and directional information. Here, taking the developing skeletal system as an example, we review our work on Wnt signaling pathways in various aspects of development. We focus particularly on our most recent findings that showed that in vertebrates, Wnt5a acts as a global cue to establishing planar cell polarity (PCP). Our work suggests that Wnt morphogens regulate development by integrating quantitative and directional information. Our work also provides important insights in disease like Robinow syndrome, brachydactyly type B1 (BDB1) and spina bifida, which can be caused by human mutations in the Wnt/PCP signaling pathway. © 2012 Yang; licensee BioMed Central Ltd.
Ritchie M.D.,Pennsylvania State University |
Holzinger E.R.,National Human Genome Research Institute |
Li R.,Pennsylvania State University |
Pendergrass S.A.,Pennsylvania State University |
Kim D.,Pennsylvania State University
Nature Reviews Genetics | Year: 2015
Recent technological advances have expanded the breadth of available omic data, from whole-genome sequencing data, to extensive transcriptomic, methylomic and metabolomic data. A key goal of analyses of these data is the identification of effective models that predict phenotypic traits and outcomes, elucidating important biomarkers and generating important insights into the genetic underpinnings of the heritability of complex traits. There is still a need for powerful and advanced analysis strategies to fully harness the utility of these comprehensive high-throughput data, identifying true associations and reducing the number of false associations. In this Review, we explore the emerging approaches for data integration-including meta-dimensional and multi-staged analyses-which aim to deepen our understanding of the role of genetics and genomics in complex outcomes. With the use and further development of these approaches, an improved understanding of the relationship between genomic variation and human phenotypes may be revealed. © 2014 Macmillan Publishers Limited. All rights reserved.
Schoenebeck J.J.,National Human Genome Research Institute |
Ostrander E.A.,National Human Genome Research Institute
Annual review of cell and developmental biology | Year: 2014
Although most modern dog breeds are less than 200 years old, the symbiosis between man and dog is ancient. Since prehistoric times, repeated selection events have transformed the wolf into man's guardians, laborers, athletes, and companions. The rapid transformation from pack predator to loyal companion is a feat that is arguably unique among domesticated animals. How this transformation came to pass remained a biological mystery until recently: Within the past decade, the deployment of genomic approaches to study population structure, detect signatures of selection, and identify genetic variants that underlie canine phenotypes is ushering into focus novel biological mechanisms that make dogs remarkable. Ironically, the very practices responsible for breed formation also spurned morbidity; today, many diseases are correlated with breed identity. In this review, we discuss man's best friend in the context of a genetic model to understand paradigms of heritable phenotypes, both desirable and disadvantageous.